Mutations in Pantothenate kinase 2 and Coenzyme A (CoA) synthase (COASY), genes involved in CoA biosynthesis, are associated with rare neurodegenerative disorders with brain iron accumulation. We showed that zebrafish pank2 gene plays an essential role in brain and vasculature development. Now we extended our study to coasy. The gene has high level of sequence identity with the human ortholog and is ubiquitously expressed from the earliest stages of development. The abrogation of its expression led to strong reduction of CoA content, high lethality and a phenotype resembling to that of dorsalized mutants...

BACKGROUND: Mitochondrial membrane protein associated neurodegeneration (MPAN) is the third most common subtype of neurodegeneration with brain iron accumulation (NBIA) and caused by mutations of the orphan gene C19ORF12 encoding a transmembrane mitochondrial protein. Like other NBIA disorders, the hallmark of neuropathology is iron deposition in the basal ganglia, but the clinical presentation is highly variable. METHODS: We present the relevant clinical history, neurological examination, electrophysiological and neuroimaging tests of a currently ten-year-old patient are presented...

INTRODUCTION: Infantile neuroaxonal dystrophy (INAD), an autosomal recessive neurodegenerative disorder due to PLA2G6 mutation, is classified both as a PLA2G6-associated neurodegeneration (PLAN) disorder and as one of the neurodegeneration with brain iron accumulation (NBIA) disorders. Age of onset and clinical presentation in INAD is variable. Typically described imaging features of cerebellar atrophy, cerebellar cortex bright FLAIR signal, and globus pallidus iron deposition are variable or late findings...

We previously demonstrated elevated brain iron levels in myelinated structures and associated cells in a hemochromatosis Hfe (-/-) xTfr2 (mut) mouse model. This was accompanied by altered expression of a group of myelin-related genes, including a suite of genes causatively linked to the rare disease family 'neurodegeneration with brain iron accumulation' (NBIA). Expanded data mining and ontological analyses have now identified additional myelin-related transcriptome changes in response to brain iron loading...

The rare, genetically determined group of diseases characterized by pathological accumulation of iron in the central nervous system and progressive, typically movement disorder's symptoms are called NBIA (neurodegeneration with brain iron accumulation). By the rapid development of molecular genetics, it has become apparent that different mutations in numerous genes can lead to pathological cerebral iron accumulation. Simultaneously, it has also been recognized that the age of onset, the symptoms and the prognosis of NBIA disorders are much more diverse than it was previously perceived...

Iron, as well as copper, is essential for a wide variety of biological processes in living organisms, however, dysregulation of iron homeostasis may lead to oxidative stress via redox cycling reactions. Therefore, cellular and systemic iron homeostasis is tightly regulated by a number of iron metabolism proteins. The brain is susceptible to iron-mediated oxidative damage because of a relatively high content of iron and high consumption of oxygen. Iron-mediated neurotoxicity is symbolically seen in neurodegeneration with brain iron accumulation (NBIA) in which iron accumulates mainly in the basal ganglia...

The use of eponyms in neurology remains controversial, and important questions have been raised about their appropriateness. Different approaches have been taken, with some eponyms being excluded, others replaced, and new ones being created. An example is Hallervorden-Spatz syndrome, which has been replaced by neurodegeneration with brain iron accuulatium (NBIA). Amiothoplic lateral sclerosys (ALS), for which the eponym is Charcot's disease, has been replaced in the USA by Lou Gehrig's disease. Guillain-Barré syndrome (GBS) is an eponym that is still the subject of controversy, and various different names are associated with it...

Neurodegeneration with brain iron accumulation (NBIA) is a heterogeneous group of single gene disorders with distinguished clinical phenotypes and definitive imaging findings. Beta propeller protein-associated neurodegeneration (BPAN) is a subentity of NBIA with X linked dominant inheritance. In this report, we describe a girl with autistic regression, seizures, intracranial calcification, iron accumulation in substantia nigra, and globi pallidi, and diagnosis of BPAN was established based on the identification of previously described disease causing variant in WD repeat domain 45 (WDR45) gene encoding for β propeller protein...

BACKGROUND: The pathophysiology underlying different types of dystonia is not yet understood. We report microelectrode data from the globus pallidus interna (GPi) and globus pallidus externa (GPe) in children undergoing deep brain stimulation (DBS) for dystonia and investigate whether GPi and GPe firing rates differ between dystonia types. METHODS: Single pass microelectrode data were obtained to guide electrode position in 44 children (3.3-18.1 years, median 10...

OBJECTIVE: Neurodegeneration with brain iron accumulation (NBIA) represents a group of inherited movement disorders characterized by iron accumulation in the basal ganglia. Recent advances have included the identification of new causative genes and highlighted the wide phenotypic variation between and within the specific NBIA subtypes. This study aimed to investigate the current status of NBIA in Korea. METHODS: We collected genetically confirmed NBIA patients from twelve nationwide referral hospitals and from a review of the literature...

Mutations in the WDR45 gene have been identified as causative for the only X-linked type of neurodegeneration with brain iron accumulation (NBIA), clinically characterized by global developmental delay in childhood, followed by a secondary neurological decline with parkinsonism and/or dementia in adolescence or early adulthood. Recent reports suggest that WDR45 mutations are associated with a broader phenotypic spectrum. We identified a novel splice site mutation (c.440-2 A > G) in a 5-year-old Argentinian patient with Rett-like syndrome, exhibiting developmental delay, microcephaly, seizures and stereotypic hand movements, and discuss this finding, together with a review of the literature...

Syndromes with neurodegeneration with brain iron accumulation (NBIA) are a group of neurodegenerative disorders characterized by abnormalities in brain iron metabolism with excess iron accumulation in the globus pallidus and to a lesser degree in the substantia nigra and sometimes adjacent areas. They clinically present as neurodegenerative diseases with progressive hypo- and/or hyperkinetic movement disorders and a variable degree of pyramidal, cerebellar, peripheral nerve, autonomic, cognitive and psychiatric involvement, and visual dysfunction...

Aberrant brain iron deposition is observed in both common and rare neurodegenerative disorders, including those categorized as Neurodegeneration with Brain Iron Accumulation (NBIA), which are characterized by focal iron accumulation in the basal ganglia. Two NBIA genes are directly involved in iron metabolism, but whether other NBIA-related genes also regulate iron homeostasis in the human brain, and whether aberrant iron deposition contributes to neurodegenerative processes remains largely unknown. This study aims to expand our understanding of these iron overload diseases and identify relationships between known NBIA genes and their main interacting partners by using a systems biology approach...

Neurodegeneration with brain iron accumulation (NBIA) refers to an inherited heterogeneous group of disorders pathologically characterized by focal brain iron deposition. Clinical phenotype, imaging findings and genotype are variable among the different types of this disorder. In this case report, we describe the imaging finding of an adolescent boy with mitochondrial membrane protein associated neurodegeneration (MPAN), a subentity of NBIA. Magnetic resonance imaging of brain revealed hypointensity of globi pallidi with medial medullary lamina appearing as a hyperintense streak in T2 weighted images...

Neurodegeneration with brain iron accumulation (NBIA) encompasses a heterogeneous group of inherited progressive neurological diseases. Beta-propeller protein-associated neurodegeneration (BPAN) has been estimated to account for ~7% of all cases of NBIA and has distinctive clinical and brain imaging findings. Heterozygous variants in the WDR45 gene located in Xp11.23 are responsible for BPAN. A clear female predominance supports an X-linked dominant pattern of inheritance with proposed lethality for germline variants in hemizygous males...